{"entity":{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","aka":[],"tldr":"Chronic inflammation is soil for cancer: it feeds growth signals, DNA damage, and immune suppression. The NF-κB switch inside cells is the master relay, and colitis, hepatitis, and H. pylori gastritis are the clinical proof.","summary":"Tumour-promoting inflammation (a hallmark enabling characteristic) acts through IL-6/STAT3, TNF/NF-κB, IL-1β, COX-2/PGE2, and inflammasome signalling. NF-κB (canonical IKK/IκB and non-canonical NIK/RelB) drives survival, cytokine production, and the SASP; it is constitutively active in many lymphomas (ABC-DLBCL via MYD88/CD79B, BTK-dependent) and myeloma. Aspirin reduces colorectal cancer in Lynch syndrome (CAPP2) and canakinumab reduced lung cancer incidence in CANTOS (secondary analysis), though as treatment it failed. Anti-inflammatory chemoprevention is one of the few validated mechanism-based preventions.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/NF-κB","links":[{"label":"Greten & Grivennikov, Inflammation and cancer: triggers, mechanisms, and consequences (Immunity 2019)","url":"https://doi.org/10.1016/j.immuni.2019.06.025"}],"tags":["mechanism"],"related":[],"cancers":["gallbladder","non-hodgkin-lymphoma"],"sections":[],"technologies":["chemoprevention","hpv-vaccine"],"targets":["btk"],"drugs":["ibrutinib","zanubrutinib"],"companies":[],"institutions":["ucsf","mskcc","dkfz"],"pathways":["jak-stat","senescence","tumor-microenvironment","cachexia-biology"],"terms":["tumor-promoting-inflammation","crs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-greten-immunity"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Karin (UCSD) on NF-κB and inflammation-driven cancer; Coussens (OHSU) on inflammation and TME; Greten (Frankfurt); CAPP2 (Burn, Newcastle)."],"analogy":"A wound that never heals: the repair crews keep pouring in growth signals and clearing away rubble, and a wound that is always being rebuilt is a wound where mistakes accumulate.","nodes":[{"id":"trig","label":"Infection, injury, obesity","x":12,"y":50},{"id":"cyto","label":"TNF, IL-1β, IL-6","x":35,"y":25},{"id":"ikk","label":"IKK → IκB degradation","x":58,"y":25},{"id":"nfkb","label":"NF-κB","x":80,"y":25},{"id":"stat3","label":"IL-6 → STAT3","x":58,"y":75},{"id":"out","label":"Survival, proliferation, SASP, immune suppression","x":92,"y":60},{"id":"btk","label":"BCR → BTK (lymphoma)","x":35,"y":75,"targetId":"btk"},{"id":"cox","label":"COX-2 → PGE2","x":12,"y":85}],"edges":[{"from":"trig","to":"cyto","type":"activates"},{"from":"cyto","to":"ikk","type":"activates"},{"from":"ikk","to":"nfkb","type":"activates"},{"from":"nfkb","to":"out","type":"activates"},{"from":"cyto","to":"stat3","type":"activates"},{"from":"stat3","to":"out","type":"activates"},{"from":"btk","to":"ikk","type":"activates"},{"from":"trig","to":"cox","type":"activates"},{"from":"cox","to":"out","type":"activates"}],"interventions":["Aspirin chemoprevention in Lynch syndrome (CAPP2); NSAIDs in FAP","BTK inhibitors (ibrutinib, zanubrutinib) shut NF-κB in CLL/lymphoma","IL-6/STAT3 blockade in cachexia and CRS (tocilizumab)","Anti-H. pylori therapy prevents gastric cancer; HBV/HCV treatment prevents HCC"]},"route":"/pathways/inflammation-nfkb/","neighbours":{"cancer":[{"id":"craniopharyngioma","kind":"cancer","name":"Craniopharyngioma","route":"/cancers/craniopharyngioma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"ependymoma","kind":"cancer","name":"Ependymoma","route":"/cancers/ependymoma/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"technology":[{"id":"chemoprevention","kind":"technology","name":"Chemoprevention & risk-reducing surgery","route":"/technologies/chemoprevention/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"}],"target":[{"id":"bcl10","kind":"target","name":"BCL10","route":"/targets/bcl10/"},{"id":"birc3","kind":"target","name":"BIRC3","route":"/targets/birc3/"},{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"card11","kind":"target","name":"CARD11","route":"/targets/card11/"},{"id":"ccr4","kind":"target","name":"CCR4","route":"/targets/ccr4/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"cd79b","kind":"target","name":"CD79b","route":"/targets/cd79b/"},{"id":"irf4","kind":"target","name":"IRF4","route":"/targets/irf4/"},{"id":"malt1","kind":"target","name":"MALT1","route":"/targets/malt1/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"},{"id":"myd88","kind":"target","name":"MYD88","route":"/targets/myd88/"},{"id":"plcg1","kind":"target","name":"PLCG1","route":"/targets/plcg1/"},{"id":"plcg2","kind":"target","name":"PLCG2","route":"/targets/plcg2/"},{"id":"prkcb","kind":"target","name":"PRKCB","route":"/targets/prkcb/"},{"id":"stat3","kind":"target","name":"STAT3","route":"/targets/stat3/"},{"id":"syk","kind":"target","name":"SYK","route":"/targets/syk/"},{"id":"tnfaip3","kind":"target","name":"TNFAIP3","route":"/targets/tnfaip3/"},{"id":"vav1","kind":"target","name":"VAV1","route":"/targets/vav1/"}],"drug":[{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"institution":[{"id":"dkfz","kind":"institution","name":"German Cancer Research Center (DKFZ)","route":"/institutions/dkfz/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"ucsf","kind":"institution","name":"UCSF Helen Diller Family Comprehensive Cancer Center","route":"/institutions/ucsf/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"cachexia-biology","kind":"pathway","name":"Cancer cachexia","route":"/pathways/cachexia-biology/"},{"id":"senescence","kind":"pathway","name":"Cellular senescence","route":"/pathways/senescence/"},{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"complement-in-cancer","kind":"pathway","name":"Complement in cancer","route":"/pathways/complement-in-cancer/"},{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"tumor-promoting-inflammation","kind":"term","name":"Enabling characteristic: tumour-promoting inflammation","route":"/terms/tumor-promoting-inflammation/"},{"id":"lymphoma-bio-ebv-latency","kind":"term","name":"Epstein-Barr virus latency programmes, and why they decide which lymphoma","route":"/terms/lymphoma-bio-ebv-latency/"},{"id":"lymphoma-bio-htlv1","kind":"term","name":"HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma","route":"/terms/lymphoma-bio-htlv1/"},{"id":"inflammation","kind":"term","name":"Inflammation","route":"/terms/inflammation/"},{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","route":"/terms/lymphoma-bio-lymphgen/"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"},{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","route":"/terms/myd88-l265p/"},{"id":"salmonella-typhi-gallbladder-cancer","kind":"term","name":"Salmonella Typhi carriage and gallbladder cancer","route":"/terms/salmonella-typhi-gallbladder-cancer/"}],"paper":[{"id":"paper-balkwill-mantovani-inflammation-virchow-lancet-2001","kind":"paper","name":"Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?","route":"/key-papers/paper-balkwill-mantovani-inflammation-virchow-lancet-2001/"},{"id":"paper-grivennikov-immunity-inflammation-cancer-cell-2010","kind":"paper","name":"Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer","route":"/key-papers/paper-grivennikov-immunity-inflammation-cancer-cell-2010/"},{"id":"paper-greten-immunity","kind":"paper","name":"Inflammation and Cancer: Triggers, Mechanisms, and Consequences","route":"/key-papers/paper-greten-immunity/"},{"id":"paper-tracerx-evolution-nature-2023","kind":"paper","name":"TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive 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